RATIONALE: Amifostine may improve blood counts in patients with myelodysplastic syndrome. Epoetin alfa may stimulate red blood cell production and be an effective treatment for anemia in patients with myelodysplastic syndrome.

PURPOSE: Phase II trial to study the effectiveness of amifostine with or without epoetin alfa in treating patients who have myelodysplastic syndrome.

Condition	Treatment or Intervention	Phase
Refractory Anemia Previously Treated Myelodysplastic Syndrome Anemia secondary myelodysplastic syndrome refractory anemia with ringed sideroblasts de novo myelodysplastic syndrome refractory anemia with excess blasts	Drug: amifostine  Drug: epoetin alfa	Phase II

Further Study Details: 

OBJECTIVES: I. Compare the effect of amifostine alone and in combination with epoetin alfa on bone marrow progenitor cells and number of blast cells, blood leukocyte counts, reticulocytes, hemoglobin level, and platelet counts as well as peripheral blood and bone marrow blast cell count in patients with myelodysplastic syndromes at a low risk of developing acute leukemia.

II. Determine partial or complete response and duration of response in this patient population.

III. Characterize the subjective and objective toxicity of amifostine in these patients.

PROTOCOL OUTLINE: This is a multicenter study.

Patients receive amifostine IV 3 times per week for 3 weeks followed by 1 week of rest. Response is assessed after 2 courses of therapy. Treatment continues in the absence of disease progression. Patients with complete response receive 1 additional course. Patients with partial response or stable disease are stratified into 2 groups:

Group 1: Patients with hemoglobin of at least 10 g/dL without transfusion receive 2 additional courses of amifostine alone.

Group 2: Patients with hemoglobin less than 10 g/dL, or who are transfusion dependent, receive 2 additional courses of amifostine in combination with epoetin alfa subcutaneously 3 times per week.

Both groups are reevaluated after these 2 additional courses. Treatment may then continue at the discretion of the treating physician.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 27-50 patients will be accrued to this study within 1.3 years.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Confirmed diagnosis of good or intermediate prognosis myelodysplasia of one of the following types: Refractory anemia; Refractory anemia with ringed sideroblasts; Refractory anemia with excess blasts with no greater than 10% bone marrow blasts
• No complex abnormalities or involvement of chromosome 7

--Prior/Concurrent Therapy--

• Biologic therapy: At least 2 months since prior growth factors or biological response modifiers for myelodysplastic syndrome except for supportive care; No other concurrent hematopoietic growth factors
• Chemotherapy: At least 2 months since other prior chemotherapy for myelodysplastic syndrome
• Endocrine therapy: No concurrent glucocorticoids; No concurrent androgens
• Radiotherapy: Not specified
• Surgery: Not specified
• Other: No concurrent vitamin A or D derivatives

--Patient Characteristics--

• Age: 18 and over
• Performance status: WHO 0-2
• Life expectancy: At least 3 months
• Hematopoietic: Hemoglobin no greater than 10 g/dL OR Transfusion requirement of at least 2 packs RBC per month AND/OR Platelet count no greater than 50,000/mm3 AND/OR Neutrophil count no greater than 1,000/mm3
• Hepatic: Bilirubin no greater than 2.5 times upper limit of normal (ULN); SGPT/ALT no greater than 2.5 times ULN
• Renal: Creatinine no greater than 1.5 times ULN
• Cardiovascular: No severe cardiac dysfunction (CTC-NCIC grade III or IV)
• Pulmonary: No severe pulmonary dysfunction
• Neurologic: No history of CNS disturbances
• Other: No current or recent history of allergies; No other nonmalignant systemic disease; Not pregnant or nursing; No active uncontrolled infections; Must have cytogenetics done within the past 4 months

Austria
      Universitaetsklinik, Innsbruck,  A-6020,  Austria
Belgium
      A.Z. St. Jan, Brugge,  8000,  Belgium
      Algemeen Ziekenhuis Middelheim, Antwerp,  2020,  Belgium
      Institut Jules Bordet, Brussels (Bruxelles),  1000,  Belgium
      Universitair Ziekenhuis Antwerpen, Edegem,  B-2650,  Belgium
Czech Republic
      Institute of Hematology and Blood Transfusion, Prague,  128 20,  Czech Republic
      Onkologicka Klinka A Onkologicka Lab, Prague (Praha),  128 08,  Czech Republic
      University Hospital - Olomouc, Olomouc,  775 20,  Czech Republic
Netherlands
      Leiden University Medical Center, Leiden,  2300 ZA,  Netherlands
Portugal
      Hospital Escolar San Joao, Porto,  4200,  Portugal
Slovakia
      Institute of Hematology & Transfusiology, University Hospital, Bratislava,  81103,  Slovakia
Switzerland
      University Hospital, Basel,  CH-4031,  Switzerland

Study chairs or principal investigators

Roel Willemze,  Study Chair,  EORTC Leukemia Cooperative Group   

Study ID Numbers:  CDR0000066783; EORTC-06975
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003681
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08